我们前期研究发现腺苷受体及其拮抗剂对中枢免疫炎症损伤有明显的调节作用。本项目旨在探讨A2aAR介导的信号通路对主导中枢炎症反应的小胶质细胞表型转换的调控作用及其机制。在国际上首次采用小胶质细胞/巨噬细胞特异性A2aAR基因敲除小鼠，叠加拮抗剂干预，分析各组别EAE表现变化与腺苷水平、A2aAR密度、相关蛋白激酶活性、小胶质细胞表型和功能的转换(M1/M2)等之间的联系；并体外培养A2aAR敲除或野生型小鼠的小胶质细胞，建立LPS-炎症细胞模型，运用腺苷、A2aAR激动剂或拮抗剂预处理，叠加蛋白激酶PKA/PKC的激动剂或拮抗剂进行干预，论证与筛查对小胶质细胞表型转换（从M1到M2）有直接双向调控作用的A2aAR相关信号通路，阐明A2aAR对中枢炎症损伤的调节作用机制。为新药研发提供新靶标。

We found the adenosine receptors and their antagonists played a prominent role in regulation for the CNS inflammatory injury in our previous study. To explore the bidirectional regulation of A2aAR-mediated signaling pathway for controlling the phenotype and function of microglia switched from M1 to M2 during EAE development and progress.For the first time, we apply the microglia/macrophage specificity A2aAR knockout mice, together with antagonist intervention, to analyze the correlation among the EAE phenotype, adenosine level, A2aAR density, related protein kinase activity and switching of the phenotype and function of microglia (M1 / M2). In addition, microglia from A2aAR knockout and wild type mice will be cultured in vitro to establish the LPS-induced inflammatory cell model. By pretreating with adenosine, A2aAR agonist and antagonist, in accompany with PKA/PKC agonist and antagonist, we will further demonstrate and screening the A2aAR signaling pathway that occupied a direct bidirection switch effect of microglia. It will offer a new target in therapeutic strategy for new drug development.